Myostatin and markers of bone metabolism in dermatomyositis.

BACKGROUND: In dermatomyostis (DM) patients, inflammation, reduced activity, and medication have a negative impact on the musculoskeletal system. Several endocrine factors are involved in muscle growth and bone turnover. OBJECTIVE: We aimed to investigate factors regulating myogenesis and bone metabolism and to evaluate possible associations between these endocrine factors, muscle strength, and functional tests in DM patients. METHODS: We conducted a cross-sectional study in 20 dermatomyositis patients. Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf 1 (Dkk1), sclerostin (SOST), periostin (PSTN), the receptor activator nuclear factor kB ligand (RANKL):osteoprotegerin (OPG) ratio and fibroblast growth factor 23 (FGF23) were determined. Physical function was evaluated by hand-held strength measurement, chair rising test, timed up and go test and the 3-min walking test. RESULTS: Serum MSTN and FGF23 levels (2.5 [1.9; 3.2] vs. 1.9 [1.6; 2.3] and 2.17 [1.45; 3.26] vs. 1.28 [0.79; 1.96], respectively; p <  0.05) were significantly higher in DM patients than in controls. Dkk1 was significantly lower (11.4 [6.9; 20.0] vs. 31.8 [14.3; 50.6], p <  0.01). Muscle strength and physical function tests correlated with each other (e.g. hip flexion - timed up and go test: r = - 0.748, p < 0.01). CONCLUSION: In DM patients, biochemical musculo-skeletal markers are altered and physical function shows deficits. All these tests reflect independent of each other different deficits in long-term DM patients which is important for the assessment of DM patients as well as planning of therapeutic interventions in clinical routine.

Bone Stress Injuries Are Associated With Differences in Bone Microarchitecture in Male Professional Soldiers.

Bone stress injuries are commonly due to repetitive loading, as often described in competitive athletes or military recruits. The underlying pathophysiology of bone stress injuries is multifactorial. The present cross-sectional study investigated (i) cortical and trabecular bone microstructure as well as volumetric bone mineral density in subjects with bone stress injuries at the tibial diaphysis, measured at the distal tibia and the distal radius by means of high-resolution peripheral quantitative computed tomography (CT), (ii) areal bone mineral density using dual-energy X-ray absorptiometry as well as calcaneal dual X-ray absorptiometry and laser, and (iii) the influence on bone turnover markers of formation and resorption at the early phase after injury. A total of 26 Caucasian male professional soldiers with post-training bone stress injury at the tibial diaphysis were included (case group). A total of 50 male, Caucasian professional soldiers from the same military institution served as controls (control group). High-resolution peripheral quantitative CT revealed a higher total area at the radius within the case group. Cortical bone mineral density was reduced at the radius and tibia within the case group. The trabecular number and trabecular thickness were reduced at the tibia in the case group. The trabecular network was more inhomogeneous at the radius and tibia within the case group. Calcaneal dual X-ray absorptiometry and laser was significantly reduced in the case group. This study quantified differences in bone microstructure among otherwise healthy individuals. Differences in bone microarchitecture may impair the biomechanical properties by increasing the susceptibility to sustain bone stress injuries. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2516-2523, 2019.

Myostatin and other musculoskeletal markers in lung transplant recipients.

Recipients of lung transplantation (LuTx) may experience impaired muscle function and bone metabolism even after rehabilitation. We investigated the potential use of musculoskeletal markers in identifying the impairment of muscle function and bone function in these patients. Biochemical parameters, bodily functions, and lung function of 37 LuTx recipients were evaluated at the time of their discharge from the hospital stay and about 6 months later. The biomarkers were also assessed in 30 healthy age and gender distribution-matched controls. Compared to controls, the negative muscle regulator myostatin was elevated in LuTx recipients at baseline and follow-up, whereas its opponent follistatin only showed a group-specific difference at follow-up. LuTx recipients had reduced serum levels of sclerostin and increased levels of dickkopf 1 and periostin. Lung function and physical function were improved during follow-up. The change in lung function was correlated with the change in chair-rising time and the 6-min walking test. At follow-up, all musculoskeletal markers of LuTx recipients differed from those of controls, thus reflecting their still reduced lung function and bodily functions. Among the tested biomarkers, myostatin, sclerostin, dickkopf 1, and periostin were useful to detect impaired musculoskeletal function in LuTx recipients. Myostatin may serve as a target of treatment in the future.

Long-Term Effects of Severe Burn Injury on Bone Turnover and Microarchitecture.

Severe burn injury triggers massive alterations in stress hormone levels with a dose-dependent hypermetabolic status including increased bone resorption. This study evaluated bone microarchitecture measured by noninvasive high-resolution peripheral quantitative computed tomography (HR-pQCT). Changes of serum bone turnover markers (BTM) as well as regulators of bone signaling pathways involved in skeletal health were assessed. Standardized effect sizes as a quantitative measure regarding the impact of serum changes and the prediction of these changes on bone microarchitecture were investigated. In total, 32 male patients with a severe burn injury (median total body surface area [TBSA], 40.5%; median age 40.5 years) and 28 matched male controls (median age 38.3 years) over a period of 24 months were included. In patients who had sustained a thermal injury, trabecular and cortical bone microstructure showed a continuous decline, whereas cortical porosity (Ct.Po) and pore volume increased. Initially, elevated levels of BTM and C-reactive protein (CRP) continuously decreased over time but remained elevated. In contrast, levels of soluble receptor activator of NF-κB ligand (sRANKL) increased over time. Osteocalcin, bone-specific alkaline phosphatase (BALP), intact N-terminal type 1 procollagen propeptide (P1NP), and cross-linked C-telopeptide (CTX) acutely reflected the increase of Ct.Po at the radius (R2 = 0.41), followed by the reduction of trabecular thickness at the tibia (R2 = 0.28). In adult male patients, early and sustained changes of markers of bone resorption, formation and regulators of bone signaling pathways, prolonged inflammatory cytokine activities in conjunction with muscle catabolism, and vitamin D insufficiency were observed. These alterations are directly linked to a prolonged deterioration of bone microstructure. The probably increased risk of fragility fractures should be of clinical concern and subject to future interventional studies with bone-protective agents. © 2017 American Society for Bone and Mineral Research.

Can Early Rehabilitation on the General Ward After an Intensive Care Unit Stay Reduce Hospital Length of Stay in Survivors of Critical Illness?: A Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate if an early rehabilitation program for survivors of critical illness improves functional recovery, reduces length of stay, and reduces hospital costs. DESIGN: This was a prospective randomized controlled trial. Fifty-three consecutive survivors of critical illness were included in the study. After discharge from the intensive care unit, the intervention group received an early rehabilitation program, and the standard-care group received physical therapy as ordered by the primary care team. Length of stay at the general ward after transfer from the intensive care unit was recorded. In addition, Early Rehabilitation Barthel Index, visual analog scale for pain, 3-minute walk test, Beck Depression Inventory, State-Trait Anxiety Inventory, and Medical Research Council scale were used. RESULTS: In the per-protocol analysis, length of stay at the general ward was a median 14 days (interquartile range [IQR], 12-20 days) in the early rehabilitation and 21 days [IQR, 13-34 days) in the standard-care group. This significant result could not be confirmed by the intention-to-treat analysis (16 days [IQR, 13-23 days] vs. 21 days [IQR, 13-34 days]). Secondary outcomes were similar between the groups. Hospital costs were lower in the intervention group. No adverse effects were detected. CONCLUSIONS: An early rehabilitation program in survivors of critical illness led to an earlier discharge from the hospital, improved functional recovery, and was also cost-effective and safe. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) delineate the benefits of early rehabilitation on a general medicine ward after an intensive care unit stay, (2) recognize the safety of appropriately implemented early rehabilitation, and (3) incorporate early rehabilitation on the general medical ward as applicable. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Is suprascapular neuropathy common in high-performance beach volleyball players? A retrospective analysis.

BACKGROUND: Pain in the shoulder is a common problem in overhead sports and at times goes along with atrophy of the supra- and infraspinatus muscles. A neuropathy of the suprascapular nerve is one possible reason. The aim of the study was to examine the suprascapular nerve in Austrian high-performance beach volleyball players. METHODS: In this cross-sectional study, 18 high-performance beach volleyball players were included. An electrophysiological examination was performed consecutively. Nerve conduction studies of the suprascapular nerve were performed bilaterally. Needle electromyography was done for the infraspinatus muscle of the dominant arm. Additionally, pain and muscle atrophy were evaluated. RESULTS: No acute or chronic neurogenic changes in the infraspinatus muscle were seen in any player, although atrophy of the suprascapularis innervated muscles was present in five players. CONCLUSIONS: A lesion of the suprascapular nerve could not be shown in any of the players. Therefore, a biomechanical cause has to be considered for the clinical symptoms in the present study population.

Identification of International Classification of Functioning, Disability and Health categories for patients with peripheral arterial disease.

OBJECTIVE: Disease-specific categories of the International Classification of Functioning, Disability and Health have not yet been described for patients with chronic peripheral arterial obstructive disease (PAD). The authors examined the relationship between the categories of the Brief Core Sets for ischemic heart diseases with the Peripheral Artery Questionnaire and the ankle-brachial index to determine which International Classification of Functioning, Disability and Health categories are most relevant for patients with PAD. DESIGN: This is a retrospective cohort study including 77 patients with verified PAD. Statistical analyses of the relationship between International Classification of Functioning, Disability and Health categories as independent variables and the endpoints Peripheral Artery Questionnaire or ankle-brachial index were carried out by simple and stepwise linear regression models adjusting for age, sex, and leg (left vs. right). RESULTS: The stepwise linear regression model with the ankle-brachial index as dependent variable revealed a significant effect of the variables blood vessel functions and muscle endurance functions. Calculating a stepwise linear regression model with the Peripheral Artery Questionnaire as dependent variable, a significant effect of age, emotional functions, energy and drive functions, carrying out daily routine, as well as walking could be observed. CONCLUSIONS: This study identifies International Classification of Functioning, Disability and Health categories in the Brief Core Sets for ischemic heart diseases that show a significant effect on the ankle-brachial index and the Peripheral Artery Questionnaire score in patients with PAD. These categories provide fundamental information on functioning of patients with PAD and patient-centered outcomes for rehabilitation interventions.

Effects of neuromuscular electrical stimulation on muscle layer thickness of knee extensor muscles in intensive care unit patients: a pilot study.

OBJECTIVE: It is known that patients in the intensive care unit show an enormous loss of muscle mass. Neuromuscular electrical stimulation is effective in enhancing strength and endurance in immobilized patients. The aim of this study was to evaluate the effects of neuromuscular electrical stimulation on muscle layer thickness of knee extensor muscles in intensive care unit patients. DESIGN: Randomized, controlled, double-blind, pilot trial. PATIENTS: Thirty-three patients, male to female ratio 26:7, mean age 55 years (standard deviation 15). METHODS: After enrolment in the study, intensive care unit patients (main diagnoses: polytrauma, cardiovascular diseases, transplantation, pneumonia, cancer) were stratified (based on the length of their stay in hospital) into 2 groups: 17 acute patients (< 7 days) and 16 long-term patients (> 14 days). Both groups were randomized to a stimulation group or a sham-stimulation group. Neuromuscular electrical stimulation was applied to knee extensor muscles for a period of 4 weeks (session time 30-60 minutes, 5 days/week). Ultrasound measurements were performed before and after the stimulation period to quantify muscle layer thickness of knee extensor muscles. RESULTS: Only stimulated long-term patients (+4.9%) showed a significant (p = 0.013) increase in muscle layer thickness compared with sham-stimulated patients (-3.2%). CONCLUSION: Neuromuscular electrical stimulation appears to be a useful adjunct to revert muscle wasting in intensive care unit long-term patients; however, larger studies with a larger sample size are needed to confirm these promising, but preliminary, results.

Diagnostic accuracy and reliability of muscle strength and endurance measurements in patients with chronic low back pain.

OBJECTIVE: Dynamometric trunk muscle strength and endurance tests are performed widely within the rehabilitation management of chronic low back pain. The aim of this study was to examine the accuracy and long-term reliability of these measurements in patients with chronic low back pain. DESIGN: Cross-sectional study. SUBJECTS: Thirty-two patients with chronic low back pain, 19 healthy controls and 15 patients with chronic headache matched for age, sex and body mass index. METHODS: Both patient groups and healthy controls performed isokinetic and isometric trunk extensor and flexor tests on a Biodex 2000 dynamometer. The Biering-Sørensen test served to examine back muscle endurance. Borg-Category-Ratio-Scales CR-10 rated participants' body experience immediately before and after the testing. Patients with chronic low back pain repeated measurements after 3 weeks. RESULTS: Among dynamometric tests, isokinetic measurements revealed the best area under the curve (AUC = 0.89) for the discrimination between patients with chronic low back pain and healthy controls. Reliability testing revealed highly significant learning effects for isometric trunk flexion and isokinetic measurements. The Biering-Sørensen test demonstrated excellent accuracy (AUC = 0.93) and no learning effects. Borg-category-ratio-scale ratings were not associated with the observed changes. CONCLUSION: In chronic low back pain dynamometric trunk muscle measures are limited to muscle function assessment purposes. Monitoring treatment outcome in these patients with these measures appears to be problematic because of learning effects. Based on our findings, we recommend the Biering-Sørensen test for management of chronic low back pain rehabilitation.

Muscle wasting in intensive care patients: ultrasound observation of the M. quadriceps femoris muscle layer.

OBJECTIVE: Patients in intensive care exhibit a high degree of loss of muscle mass. Appropriate instruments are needed to document muscle wasting in these patients. The aim of this pilot study was to describe muscle wasting in patients in the intensive care unit. DESIGN: Two-fold study setting: prospective longitudinal and cross-sectional single-blind. PATIENTS: A total of 118 patients in the intensive care unit (length of stay 1-98 days; male:female ratio 88:30; age 55 +/- 17 years) were included in a two-fold study setting. METHODS: Muscle layer thickness of the M. quadriceps femoris was documented using ultrasound measurement at well-defined points. Seventeen pilot-patients were measured twice; at baseline and after 28 days. In another group of 101 patients, muscle layer thickness was determined once after a random length of stay. The results of both groups were compared and correlated. RESULTS: In both groups, M. quadriceps femoris thickness showed a significant negative correlation with length of stay in the intensive care unit (p < 0.01). Furthermore, muscle wasting in intensive care patients could be described using a logarithmic function. CONCLUSION: Loss of muscle mass shows a negative correlation with length of stay, and seems to be higher during the first 2-3 weeks of immobilization/intensive care unit stay. Ultrasound is a valid and practical measurement tool for documenting muscle mass (e.g. muscle layer thickness) as part of the daily routine at an intensive care unit.

Improved postural control after computerized optokinetic therapy based on stochastic visual stimulation in patients with vestibular dysfunction.

Balance is accomplished by the congruent integration of visual, vestibular and somatosensory input and the execution of adequate control movements. With increasing age, nonlinear dynamics of central control systems become more regular. In unilateral vestibular dysfunction, sensory input to central systems is similarly less complex, because of one sided reduction of information influx. This study aimed to increase postural stability in patients with vestibular asymmetry and resulting disequilibrium by implementing a computerized visual training method relying on the principles of stochastic resonance. 24 subjects (average age 64a, 31-78a, 15 women, 9 men), with minimum 3 months of persisting disequilibrium due to vestibular dysfunction, were either treated with computerized optokinetic therapy (COKT), or solely observed. Treated patients were requested to read texts, stochastically moving in a previously defined matrix, during 10 sessions over three weeks. The Sensory Organization Test (SOT) was used for comparative posturographic measurements. COKT patients showed significant improvement in conditions 4, 6 and composite score. A significant post-therapeutic difference was seen between therapy and control groups in conditions 1, 6 and composite score. The results show a clinical benefit and we conclude COKT to be an effective rehabilitation method in patients with chronic disequilibrium.